We hypothesize that UDCA on top of ezetimibe leads to an increased cholesterol excretion via the feces by stimulating ABCG5/8 and preventing absorption of cholesterol due to blocking NPC1L1 and therefore promoting elimination of cholesterol from the…
Bron
Verkorte titel
Aandoening
Hypercholesterolemia, fecal cholesterol excretion, ABCG5/8, NPC1L1, trans-intestinal cholesterol excretion
Ondersteuning
Onderzoeksproduct en/of interventie
Geen registraties gevonden.
Uitkomstmaten
Primaire uitkomstmaten
Total faecal sterol concentration (faecal total neutral sterol concentration (FNS) + faecal bile acid concentration)
Achtergrond van het onderzoek
Intestinal cholesterol secretion is mediated via the ATP binding cassette (ABC) half transporters G5 and G8 (ABCG5/G8) while cholesterol absorption is mediated by the Niemann-Pick C1 Like (NPC1L1) protein, which is inhibited by ezetimibe. There is growing evidence that hydrophilic bile acids like ursochol (ursodeoxycholic acid, UDCA) promote ABCG5/G8 activity in mice.
The primary objective is to evaluate the effect of UDCA and ezetimibe on cholesterol elimination assessed as total faecal sterol concentration. Secondary objective is to assess the effect of UDCA and ezetimibe on plasma lipid profile/composition.
The current study is an investigator initiated, single-centre, randomized, double blind, placebo-controlled , cross-over, proof of concept study, to explore the translational relevance of UDCA on top of ezetimibe on cholesterol elimination.
Doel van het onderzoek
We hypothesize that UDCA on top of ezetimibe leads to an increased cholesterol excretion via the feces by stimulating ABCG5/8 and preventing absorption of cholesterol due to blocking NPC1L1 and therefore promoting elimination of cholesterol from the body.
Onderzoeksopzet
Visit 1 (Day 0): Screening
Visit 2 (Day 21): Randomization
Visit 3 (Day 35): end of treatment period 1 + start washout period
Visit 4 (Day 56): start treatment period 2
Visit 5 (Day 70): end of treatment period 2 + end of study
Onderzoeksproduct en/of interventie
Ursodeoxycholicacid (UDCA) 600mg once daily or placebo
Background therapy: ezetimibe 10mg once daily
Publiek
Wetenschappelijk
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
- Hypercholesterolemia, with LDL plasma levels >2.6 mmol/L
- Body mass index (BMI) ¡Ý19 ¡Ü30 kg/m2
- Use of statin therapy (stable dose for 3 months) or no statin therapy at all
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
- Medical, surgical, laboratory or other conditions, which in the judgment of the Physician Investigator would make the subject unsuitable for enrollment, or potentially interfere with subject participation or completion of the study
- Suffering from an inflammatory bowel disease, e.g. Crohn¡¯s disease or ulcerative colitis.
- Suffering from gall stones or another biliary disease.
- Suffering diabetes mellitus (type I or II).
- Recent history of, or current drug or alcohol abuse
- AST or ALT levels > 2 x ULN
- Unable or unwilling to comply with the protocol requirements or deemed by the investigator to be unfit for the study.
- Presence of contra indications for the use of UDCA and ezetimibe (see SPC)
- Use of lipid lowering drugs such as the following:
o Statins and fibrates unless on a stable dose for at least 3 months prior to screening
o Use of nicotinic acid or derivates of nicotinic acid within 4 weeks prior to screening
o Use of cholestyramine or colestipol
- Use of other drugs such as the following:
o Ciclosporine
o Antacids containing aluminium hydroxide or aluminium oxide
- Likely to leave the study before its completion
- Participation in other intervention studies
Opzet
Deelname
Voornemen beschikbaar stellen Individuele Patiënten Data (IPD)
Opgevolgd door onderstaande (mogelijk meer actuele) registratie
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Andere (mogelijk minder actuele) registraties in dit register
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In overige registers
Register | ID |
---|---|
NTR-new | NL6932 |
NTR-old | NTR7128 |
CCMO | NL56321.018.16 |